Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia

被引：0

作者：

Jayaram Vijayakrishnan

James Studd

Peter Broderick

Ben Kinnersley

Amy Holroyd

Philip J. Law

Rajiv Kumar

James M. Allan

Christine J. Harrison

Anthony V. Moorman

Ajay Vora

Eve Roman

Sivaramakrishna Rachakonda

Sally E. Kinsey

Eamonn Sheridan

Pamela D. Thompson

Julie A. Irving

Rolf Koehler

Per Hoffmann

Markus M. Nöthen

Stefanie Heilmann-Heimbach

Karl-Heinz Jöckel

Douglas F. Easton

Paul D. P. Pharaoh

Alison M. Dunning

Julian Peto

Frederico Canzian

Anthony Swerdlow

Rosalind A. Eeles

ZSofia Kote-Jarai

Kenneth Muir

Nora Pashayan

Mel Greaves

Martin Zimmerman

Claus R. Bartram

Martin Schrappe

Martin Stanulla

Kari Hemminki

Richard S. Houlston

机构：

[1] The Institute of Cancer Research,Division of Genetics and Epidemiology

[2] German Cancer Research Centre,Division of Molecular Genetic Epidemiology

[3] Newcastle University,Northern Institute for Cancer Research

[4] Newcastle University,Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research

[5] Great Ormond Street Hospital,Department of Haematology

[6] University of York,Department of Health Sciences

[7] Leeds General Infirmary,Department of Paediatric and Adolescent Haematology and Oncology

[8] University of Leeds,Medical Genetics Research Group, Leeds Institute of Molecular Medicine

[9] St. Mary’s Hospital,Paediatric and Familial Cancer Research Group, Institute of Cancer Sciences

[10] University of Heidelberg,Department of Human Genetics, Institute of Human Genetics

[11] University of Bonn,Department of Genomics, Institute of Human Genetics, Life & Brain Centre

[12] University Hospital and University of Basel,Department of Biomedicine, Human Genomics Research Group

[13] University of Duisburg–Essen,Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen

[14] University of Cambridge,Department of Oncology, Centre for Cancer Genetic Epidemiology

[15] University of Cambridge,Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology

[16] University of Cambridge,Department of Oncology, Centre for Cancer Genetic Epidemiology

[17] Strangeways Laboratory,Department of Non

[18] London School of Hygiene and Tropical Medicine,Communicable Disease Epidemiology

[19] German Cancer Research Center (DKFZ),Genomic Epidemiology Group

[20] The Institute of Cancer Research,Division of Breast Cancer Research

[21] Royal Marsden NHS Foundation Trust,Institute of Population Health

[22] University of Manchester,Warwick Medical School

[23] University of Warwick,Department of Applied Health Research

[24] University College London,Centre for Evolution and Cancer

[25] Institute of Cancer Research,Department of Paediatric Haematology and Oncology

[26] Hannover Medical School,General Paediatrics

[27] University Hospital Schleswig-Holstein,Center for Primary Health Care Research

[28] Lund University,Department of Preventive Medicine, Keck School of Medicine

[29] University of Southern California/Norris Comprehensive Cancer Center,Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, Strangeways Research Laboratory

[30] University of Cambridge,Department of Epidemiology and Biostatistics

[31] The Institute of Cancer Research,Seidman Cancer Center

[32] Case Western Reserve University,Department of Clinical Neurosciences

[33] University Hospitals,Division of Cancer Epidemiology and Genetics

[34] University of Cambridge,Department of Medical Epidemiology and Biostatistics

[35] National Cancer Institute,Epidemiology Research Program

[36] NIH,SWOG Statistical Center

[37] Karolinska Institute,Australian Prostrate Cancer BioResource (APCB), Australian Prostate Cancer Research Centre

[38] American Cancer Society,Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science

[39] Fred Hutchinson Cancer Research Center,Department of Medical Biochemistry and Genetics, Institute of Biomedicine

[40] Queensland University of Technology,Tyks Microbiology and Genetics, Department of Medical Genetics

[41] Translational Research Institute,BioMediTech

[42] University of Turku,Division of Nutritional Epidemiology, Institute of Environmental Medicine

[43] Turku University Hospital,Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research

[44] University of Tampere,Department of Epidemiology

[45] Karolinska Institutet,Department of Molecular Medicine

[46] The Christie Hospital NHS Foundation Trust,Department of Clinical Medicine

[47] Harvard School of Public Health,Department of Medical Genetics

[48] CeRePP,Department of Oncology, Addenbrooke’s Hospital

[49] Pitie-Salpetriere Hospital,Li Ka Shing Centre

[50] UPMC Univ Paris 06,Cancer Epidemiology, Nuffield Department of Population Health

来源：

Nature Communications | / 9卷

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摘要：

Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10−9, odds ratio (OR) = 1.34) and for ETV6-RUNX1 fusion-positive BCP-ALL at 2q22.3 (rs17481869, P = 3.20 × 10−8, OR = 2.14). Our findings provide further insights into genetic susceptibility to ALL and its biology.

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